Mast cell gene signature enrichment associates with late-onset severe asthma

Rationale: Unbiased discovery of gene signatures in sputum in the U-BIOPRED cohort revealed a possible role for mast cell gene expression in adult-onset severe asthma [Hekking et al , ERS 2015]. Therefore, we aimed to investigate whether enrichment scores of a mast cell gene signature (ESM) associate with phenotypic characteristics of adult-onset severe asthma. Methods: Patients with adult-onset severe asthma (onset ≥18yr) were selected from the U-BIOPRED cohort. ESM were calculated with Gene Set Variation Analysis (GSVA) based on expression of a set of 6 genes associated with mast cells. Clinical and inflammatory characteristics were compared between patients with high and low ESM (Fig.), using student t-tests, chi-square or Mann-Whitney U tests. Results: Patients with high ESM (n=33) were significantly older when asthma was first diagnosed (mean±SD; 43.2±14.3 vs 34.2±9.7 yr; P=0.02) and had higher % eosinophils in blood (median(IQR); 20.7(4.5-42.0) vs 1.2 (0.2-2.5); P e.g. age, gender and BMI) were not significantly different between the groups. Conclusion: These results reveal two distinct subphenotypes of adult-onset severe asthma based on high and low mast cell gene signature enrichment. Their association with age-of-onset and eosinophilia may have implications for clinical management and identification of endotypes. U-BIOPRED is funded by IMI (grant 115010)